2. Academic Validation
  3. Addiction to Golgi-resident PI4P synthesis in chromosome 1q21.3-amplified lung adenocarcinoma cells

Addiction to Golgi-resident PI4P synthesis in chromosome 1q21.3-amplified lung adenocarcinoma cells

  • Proc Natl Acad Sci U S A. 2021 Jun 22;118(25):e2023537118. doi: 10.1073/pnas.2023537118.
Lei Shi 1,  Xiaochao Tan 1,  Xin Liu 1,  Jiang Yu 1,  Neus Bota-Rabassedas 1,  Yichi Niu 2 3,  Jiayi Luo 2 4,  Yuanxin Xi 5,  Chenghang Zong 2,  Chad J Creighton 5 6 7,  Jeffrey S Glenn 8 9,  Jing Wang 5,  Jonathan M Kurie 10
Affiliations

Affiliations

  • 1 Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030.
  • 2 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030.
  • 3 Genetics and Genomics Graduate Program, Baylor College of Medicine, Houston, TX 77030.
  • 4 Cancer and Cell Biology Graduate Program, Baylor College of Medicine, Houston, TX 77030.
  • 5 Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030.
  • 6 Department of Medicine, Baylor College of Medicine, Houston, TX 77030.
  • 7 Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030.
  • 8 Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305.
  • 9 Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305.
  • 10 Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030; [email protected].
PMID: 34155143 DOI: 10.1073/pnas.2023537118
Abstract

A chromosome 1q21.3 region that is frequently amplified in diverse Cancer types encodes phosphatidylinositol (PI)-4 kinase IIIβ (PI4KIIIβ), a key regulator of secretory vesicle biogenesis and trafficking. Chromosome 1q21.3-amplified lung adenocarcinoma (1q-LUAD) cells rely on PI4KIIIβ for Golgi-resident PI-4-phosphate (PI4P) synthesis, prosurvival effector protein secretion, and cell viability. Here, we show that 1q-LUAD cells subjected to prolonged PI4KIIIβ antagonist treatment acquire tolerance by activating an miR-218-5p-dependent competing endogenous RNA network that up-regulates PI4KIIα, which provides an alternative source of Golgi-resident PI4P that maintains prosurvival effector protein secretion and cell viability. These findings demonstrate an addiction to Golgi-resident PI4P synthesis in a genetically defined subset of cancers.

Keywords

Golgi; cancer; lipids; oncogene addiction.

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